Technical Field
The present disclosure relates to a method for treating adenoid cystic carcinoma (ACC), especially tracheal adenoid cystic carcinoma (TACC), in a subject by a pharmaceutical composition containing the benzenesulfonamide derivatives.
Description of Related Art
Adenoid cystic carcinoma (ACC) is a rare form of adenocarcinoma, which is a broad term describing any cancer that begins in glandular tissues. ACC most commonly occurs in the salivary glands, but may also arise in a wide range of other locations (exocrine glands) including, for example, the breast, lacrimal gland, and in the cervix, vulva, skin (including ceruminal glands of the ear), prostate, and tracheobronchial tree. Due to the distinctive morphology and histogenesis, ACC are completely different from other tumors which are mainly consisted of squamous cell carcinomas (SCC) in clinical presentation, clinical outcome, treatment, and response to treatment.
Ninety percent of tracheal cancer in adults is malignant. Among malignant tracheal tumor, squamous cell carcinoma represents the most frequent histology (44%-63%), while tracheal adenoid cystic carcinoma (TACC) accounts for 7%-16% of the cases (Ann Otolaryngol Rhinol 2015, 3:1079). TACC originates from the submucosal glands of the airway, and ultimately one-third of TACC cause malignant airway obstruction (MAO) with associated symptoms (Adv Ther 2014, 31:512-538), which is a potential life-threatening condition.
Primary cancer of the trachea is a relatively rare and accounts for only 0.1%-0.4% of all newly diagnosed respiratory tract cancers, which corresponds to 2.6 new cases per 1,000,000 individuals annually worldwide, and less than 2 per million persons per year in the United States (equivalent to 641 persons per year in 2015's US population) (J Thorac Cardiovasc Surg 1996, 112:1522-1531). It is shown that the prevalence of TACC is less than 100 per year and therefore being designated as a rare disease.
According to previous epidemiology and health statistics, smoking remains the major risk factor of SCC, but it does not seem to affect the incidence of TACC. The delay in diagnosis of TACC often occurs because the pulmonary fields remain normal on a chest radiograph (Chest 1999, 116:803-807); and patients with TACC usually present with symptoms such as coughing, wheezing and dyspnea and are often treated for asthma for months to years before being correctly diagnosed (Mayo Clin Proc 1993, 68: 680-684).
TACC is generally considered to be a low grade malignancy, but it tends to metastasize to distant sites and often recurs after a long interval (Chang Gung Med J 2005, 28:357-363). The survival is frequently less than 2 years with distal metastasis (Cancer 1994, 73:1390-1397). ACC spreads most commonly by direct extension, submucosal or perineural invasion, or hematogenous metastasis. Pulmonary metastasis is the most common, and metastasis to the brain, bone, liver, kidney, abdomen, and hearts have been reported (J Thorac Cardiovasc Surg 1996, 111:808-913; Am J Surgery 1982, 143:697-699; Cancer 1970, 25:1448-1456).
In the early stage of the disease, primary treatment includes surgery with optional postoperative radiotherapy (RT). With the combined therapy, the 5-year overall survival (OS) rate reaches up to 52% in TACC (Int J Radiat Oncol Biol Phys 2008, 72:410-414; Ann Thorac Surg 1990, 49:69-77). However, resection is often difficult if there is invasion of adjacent critical tissues especially in patients with distal tracheal involvement (Am J Otolaryngol 2012, 33:226-231; Cancer/Radiotherapie 2005, 33:226-231), or tumors are too large to permit surgery. The complete resection rate is reported to 42%-57% (Ann Thorac Cardiovasc Surg 2002, 8:74-77). Negative surgical margins are difficult to obtain because of the relative inability to resect more than 6 cm of the trachea, and thus TACC are prone to local recurrence (Am J Otolaryngol 2012, 33:226-231).
Radiotherapy (RT) is used as the primary modality in unresectable TACC. However, TACC exhibits a limited response to chemotherapy and RT (Ann Otolaryngol Rhinol 2015, 3:1079). Compared to 52% of 5-year survival rate of resected patients, the unresectable patients (subjected to only radiotherapy) have a lower survival rate (33% in 5 years) (Ann Thorac Surg 2004, 78:1889-1897).
In general, current therapies do not possess sufficient tumor/normal tissue selectivity, and thus the efficacy is limited in infiltrative lesions commonly seen in TACC (Pan Afr Med J 2014, 19:32). On the other hand, the FDA-designated orphan drug for adenoid cystic carcinoma, Dovitinib, a multi-targeted kinase inhibitor, shows modest antitumor activity in the treatment of TACC. However, a complete treatment cycle takes 8 weeks, and nearly 94% of the patients in the clinical study had stable disease outcome (Cancer 2015, 121:2612-2617), which would hardly be satisfactory in the life-threatening airway obstruction condition. Therefore, there is a need in TACC patients for a therapy to provide tumor clearance as efficient as physical therapy/resection, and as specific as targeted therapy.
Toluene sulfonamide is known as an effective anti-fungal agent and used to treat plant and animal (e.g., human) tissues infected with a fungus. U.S. Pat. No. 5,891,454 and U.S. Pat. No. 6,727,287 both disclose a sulfonamide-containing composition that exhibits anti-cancer and anti-tumor necrotizing activity. However, there is still a need in the art for providing an injectable composition which provides sustained concentration of toluene sulfonamide and long acting effects for treating cancers.